Saturday, July 08, 2006

More about genetic engineering

Scientific American has a nice article on attempts to make Genetic Engineering more like engineering integrated circuits. One of the authors is James Collins, a former electrical engineer who now works on sythetic biology, and was profiled by Scientific American.

For the software engineers among us, how are they going about this? Through abstraction, and re-use, of course! Hope they are more successful than the software engineers.

There is a nice illustration of the different levels of abstraction in genetic engineering, and even a "Hello world" implemented with bacteria. :-)

They have a long way to go.

In living organisms, biological machinery composed of enzymes such as polymerase is able to manufacture and repair DNA molecules at speeds of up to 500 bases a second, with error rates of about one base in a billion. That represents a trillionfold performance improvement in yield throughput output divided by error rate) over the best DNA synthesis machines, which add a base every 300 seconds.

But this is cool:

What we mean by that term is well illustrated by Elowitz and Leibler’s ring oscillator, which they began as an attempt to build a synthetic biological clock, hoping that it would provide insight into the clocks that exist naturally in biological systems.Their basic circuit consisted of a DNA ring called a plasmid containing three genes: tetR, lacI and λ cI, which encode the proteins TetR, LacI and λ cI, respectively. For any gene to be translated into a protein, the enzyme polymerase must first bind to a region of the DNA strand called a promoter that lies upstream of the gene. Polymerase then transcribes the gene into messenger RNA, which in turn is translated into a protein. If polymerase cannot bind the promoter, the gene is not translated and the protein is not made. Elowitz and Leibler arranged for the protein products of the three genes in their circuit to selectively bind to one an-other’s promoter regions. Thus, the LacI protein would bind the tetR promoter, whereas the λ cI protein would bind the lacI gene’s promoter, and TetR would bind the promoter of the λ cI gene. These interrelations enable the protein product of one gene to block polymerase from binding to the promoter of another gene. Manufacture of the three proteins consequently happens in an oscillatory cycle: an abundance of LacI protein represses tetR gene activity; the absence of TetR protein then allows the λ cI gene to be turned on, which has the effect of repressing LacI production, and so on. When one of the protein products in this cycle is also linked to a gene for making a green fluorescent protein and the entire circuit is inserted into bacteria, the oscillation of this device can be observed as the bacteria blink on and off like holiday lights.

And

Inspired by these early examples, one of us (Endy), along with Knight and our M.I.T. colleague Randy Rettberg, is developing a library of biological components similar to the libraries available to chip designers. This Registry of Standard Biological Parts should facilitate a wide range of biological building projects, and our hope is that others will contribute new entries. So far the registry contains more than 1,000 individual BioBricks, as we call them, including many parts analogous to electronics, such as inverters, switches, counters, amplifiers, and components that can receive input or output a display. We have also defined a standard signal carrier—polymerase per second, or PoPS—akin to the current in a wire connecting two electronic components, so that bio fab engineers can more easily combine and reuse genetic devices.